pharmacodynamic and pharmacokinetic dose ranging study of tiotropium bromide administered via respimat device in patients with chronic obstructive pulmonary disease (copd)

Conditions: Pulmonary Disease, Chronic Obstructive

Summary: this pharmacodynamic and pharmacokinetic dose-ranging study aims to determine the optimal dose of tiotropium inhaled as a solution from a respimat device once a day for three weeks in patients with copd.


Eligibility criteria:
inclusion criteria: 1. age: ≥ 40 years; 2. diagnosis of copd and met the following criteria: 1. relatively stable, moderate to severe airway obstruction, 2. baseline 30% ≤ fev1 ≤ 65% of predicted normal value, predicted normal values are based on the guidelines for standardized lung function testing of the european community for coal and steel (eccs) , 3. baseline fev1/ forced expiratory vital capacity (fevc) ≤ 70%; 3. smoking history ≥ 10 pack-years (p.y.). a p.y. is defined as the equivalent of smoking one pack of cigarettes per day for one year; 4. male of female; 5. ability to be trained in the proper use of respimat and handihaler; 6. ability to be trained in the performance of technically satisfactory pulmonary function tests; 7. ability to provide written informed consent 8. patient affiliated to the social security system exclusion criteria: 1. history of asthma, allergic rhinitis or atopy or who have a blood eosinophil count above 600/mm³ 2. changes in the therapeutic (pulmonary) plan within the last six weeks prior to the screening visit; 3. treatment by cromolyn/nedocromil sodium; 4. treatment by antihistamines (h1 receptor antagonists); 5. a lower respiratory tract infection or any exacerbation in the past six weeks prior to the screening visit; 6. regular use of daytime oxygen therapy; 7. treatment by oral corticosteroid medication if initiated or modified within the last six weeks or if daily dose \> 10 mg prednisone equivalent; 8. history of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis 9. patients who have undergone thoracotomy with pulmonary resection; 10. history of clinically significant cardiovascular, renal neurologic, liver or endocrine dysfunction. a clinically significant disease was defined as one which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study. 11. patients with a recent (≤ one year) history of myocardial infarction, of heart failure or patients with any cardiac arrhythmia requiring drug therapy; 12. tuberculosis with indication for treatment; 13. history of cancer within the last five years. patients with treated basal cell carcinoma were allowed: 14. current psychiatric disorders; 15. patients with known symptomatic prostatic hypertrophy or bladder neck obstruction; 16. patients with any history of glaucoma or increased intra-ocular pressure; 17. patients with clinically significant abnormal baseline haematology or blood chemistry, if the abnormality defines a disease listed as an exclusion criterion; 18. patients with 1. glutamyl-oxalo-acetic transaminase/glutamyl-pyruvic transaminase (sgot/sgpt): \> 200% of the upper limit of the normal range (uln, ) 2. bilirubin: \> 150% of the uln, 3. creatinine: \> 125% of the uln; 19. intolerance to aerosolised anticholinergic containing products, and/or hypersensitivity to benzalkonium chloride, to lactose or any other components of the inhalation capsule delivery system; 20. beta-blocker medication; 21. concomitant or recent (within the last month) use of investigational drugs; 22. history of drug abuse and/or alcoholism; 23. pregnant or nursing women and women of childbearing potential not using a medically approved means of contraception ( urinary pregnancy test at screening); 24. previous participation in this study (i.e. having been allocated a randomised treatment number); 25. patients deprived of their freedom by a judicial or administrative decision; 26. minors, adults under guardianship; 27. persons in medical or social establishments; 28. patients in emergency situations